Tag: hemostats

An important determinant of “where medicine will be” in 2035 is the set of dynamics and forces behind healthcare delivery systems, including primarily the payment method, especially regarding reimbursement. It is clear that some form of reform in healthcare will result in a consolidation of the infrastructure paying for and managing patient populations. The infrastructure is bloated and expensive, unnecessarily adding to costs that neither the federal government nor individuals can sustain. This is not to say that I predict movement to a single payer system — that is just one perceived solution to the problem. There are far too many costs in healthcare that offer no benefits in terms of quality; indeed, such costs are a true impediment to quality. Funds that go to infrastructure (insurance companies and other intermediaries) and the demands they put on healthcare delivery work directly against quality of care. So, in the U.S., whether Obamacare persists (most likely) or is replaced with a single payer system, state administered healthcare (exchanges) or some other as-yet-unidentified form, there will be change in how healthcare is delivered from a cost/management perspective.

From the clinical practice and technology side, there will be enormous changes to healthcare. Here are examples of what I see from tracking trends in clinical practice and medical technology development:

Cancer 5 year survival rates will, for many cancers, be well over 90%. Cancer will largely be transformed in most cases to chronic disease that can be effectively managed by surgery, immunology, chemotherapy and other interventions. Cancer and genomics, in particular, has been a lucrative study (see The Cancer Genome Atlas). Immunotherapy developments are also expected to be part of many oncology solutions. Cancer has been a tenacious foe, and remains one we will be fighting for a long time, but the fight will have changed from virtually incapacitating the patient to following protocols that keep cancer in check, if not cure/prevent it.

Diabetes Type 1 (juvenile onset) will be managed in most patients by an “artificial pancreas”, a closed loop glucometer and insulin pump that will self-regulate blood glucose levels. OR, stem cell or other cell therapies may well achieve success in restoring normal insulin production and glucose metabolism in Type 1 patients. The odds are better that a practical, affordable artificial pancreas will developed than stem or other cell therapy, but both technologies are moving aggressively and will gain dramatic successes within 20 years.

Developments in the field of the “artificial pancreas” have recently gathered considerable pace, such that, by 2035, type 1 blood glucose management may be no more onerous than a house thermostat due to the sophistication and ease-of-use made possible with the closed loop, biofeedback capabilities of the integrated glucometer, insulin pump and the algorithms that drive it, but that will not be the end of the development of better options for type 1 diabetics. Cell therapy for type 1 diabetes, which may be readily achieved by one or more of a wide variety of cellular approaches and product forms (including cell/device hybrids) may well have progressed by 2035 to become another viable alternative for type 1 diabetics.

Diabetes Type 2 (adult onset) will be a significant problem governed by different dynamics than Type 1. A large body of evidence will exist that shows dramatically reduced incidence of Type 2 associated with obesity management (gastric bypass, satiety drugs, etc.) that will mitigate the growing prevalence of Type 2, but research into pharmacologic or other therapies may at best achieve only modest advances. The problem will reside in the complexity of different Type 2 manifestation, the late onset of the condition in patients who are resistant to the necessary changes in lifestyle and the global epidemic that will challenge dissemination of new technologies and clinical practices to third world populations.

Despite increasing levels of attention being raised to the burden of type 2 worldwide, including all its sequellae (vascular, retinal, kidney and other diseases), the pace of growth globally in type 2 is still such that it will represent a problem and target for pharma, biotech, medical device, and other disciplines.

Cell therapy and tissue engineering will offer an enormous number of solutions for conditions currently treated inadequately, if at all. Below is an illustration of the range of applications currently available or in development, a list that will expand (along with successes in each) over the next 20 years.

Cell therapy will have deeply penetrated virtually every medical specialty by 2035. Most advanced will be those that target less complex tissues: bone, muscle, skin, and select internal organ tissues (e.g., bioengineered bladder, others). However, development will have also followed the money. Currently, development and use of conventional technologies in areas like cardiology, vascular, and neurology entails high expenditure that creates enormous investment incentive that will drive steady development of cell therapy and tissue engineering over the next 20 years, with the goal of better, long-term and/or less costly solutions.

Gene therapy will be an option for a majority of genetically-based diseases (especially inherited diseases) and will offer clinical options for non-inherited conditions. Advances in the analysis of inheritance and expression of genes will also enable advanced interventions to either ameliorate or actually preempt the onset of genetic disease.As the human genome is the engineering plans for the human body, it is a potential mother lode for the future of medicine, but it remains a complex set of plans to elucidate and exploit for the development of therapies. While genetically-based diseases may readily be addressed by gene therapies in 2035, the host of other diseases that do not have obvious genetic components will resist giving up easy gene therapy solutions. Then again, within 20 years a number of reasonable advances in understanding and intervention could open the gate to widespread “gene therapy” (in some sense) for a breadth of diseases and conditions –> Case in point, the recent emergence of the gene-editing technology, CRISPR, has set the stage for practical applications to correct genetically-based conditions.

Drug development will be dramatically more sophisticated, reducing the development time and cost while resulting in drugs that are far more clinically effective (and less prone to side effects). This arises from drug candidates being evaluated via distributed processing systems (or quantum computer systems) that can predict efficacy and side effect without need of expensive and exhaustive animal or human testing.The development of effective drugs will have been accelerated by both modeling systems and increases in our understanding of disease and trauma, including pharmacogenomics to predict drug response. It may not as readily follow that the costs will be reduced, something that may only happen as a result of policy decisions.

Most surgical procedures will achieve the ability to be virtually non-invasive. Natural orifice transluminal endoscopic surgery (NOTES) will enable highly sophisticated surgery without ever making an abdominal or other (external) incision. Technologies like “gamma knife” and similar will have the ability to destroy tumors or ablate pathological tissue via completely external, energy-based systems.By 2035, technologies such as these will measurably reduce inpatient stays, on a per capita basis, since a significant reason for overnight stays is the trauma requiring recovery, and eliminating trauma is a major goal and advantage of minimally invasive technologies (e.g., especially the NOTES technology platform). A wide range of other technologies (e.g., gamma knife, minimally invasive surgery/intervention, etc.) across multiple categories (device, biotech, pharma) will also have emerged and succeeded in the market by producing therapeutic benefit while minimizing or eliminating collateral damage.

Information technology will radically improve patient management. Very sophisticated electronic patient records will dramatically improve patient care via reduction of contraindications, predictive systems to proactively manage disease and disease risk, and greatly improve the decision-making of physicians tasked with diagnosing and treating patients.There are few technical hurdles to the advancement of information technology in medicine, but even in 2035, infotech is very likely to still be facing real hurdles in its use as a result of the reluctance in healthcare to give up legacy systems and the inertia against change, despite the benefits.

Personalized medicine. Perfect matches between a condition and its treatment are the goal of personalized medicine, since patient-to-patient variation can reduce the efficacy of off-the-shelf treatment. The thinking behind gender-specific joint replacement has led to custom-printed 3D implants. The use of personalized medicine will also be manifested by testing to reveal potential emerging diseases or conditions, whose symptoms may be ameliorated or prevented by intervention before onset.

Systems biology will underlie the biology of most future medical advances in the next 20 years. Systems biology is a discipline focused on an integrated understanding of cell biology, physiology, genetics, chemistry, and a wide range of other individual medical and scientific disciplines. It represents an implicit recognition of an organism as an embodiment of multiple, interdependent organ systems and its processes, such that both pathology and wellness are understood from the perspective of the sum total of both the problem and the impact of possible solutions.This orientation will be intrinsic to the development of medical technologies, and will increasingly be represented by clinical trials that throw a much wider and longer-term net around relevant data, staff expertise encompassing more medical/scientific disciplines, and unforeseen solutions that present themselves as a result of this approach.Other technologies being developed aggressively now will have an impact over the next twenty years, including medical/surgical robots (or even biobots), neurotechnologies to diagnose, monitor, and treat a wide range of conditions (e.g., spinal cord injury, Alzheimer’s, Parkinson’s etc.).

The breadth and depth of advances in medicine over the next 20 years will be extraordinary, since many doors have been recently opened as a result of advances in genetics, cell biology, materials science, systems biology and others — with the collective advances further stimulating both learning and new product development.

See the 2016 report #290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.”

See the published report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”.

Sealants, glues, and hemostats must offer benefit to be adopted in clinical practice, or surgical procedures. Benefits can fall into a number of categories. These range from preventing serious complications from surgery (blood loss), improved patient outcomes (fewer complications, reduction in repeats), reductions in procedure time or other time- or cost-saving benefits, or improved aesthetic and perceived benefits. See these detailed below.

Criteria for Adjunctive Use of Hemostats, Sealants, Glues and Adhesion Prevention Products in Surgery

See the published report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”.

See Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”. (Note: This report has been superceded by the August 2016 Report #S290.)

Sutures have been in use for potentially thousands of years, and staples for the last several decades. Both have been frequently been the target of new development in wound closure and management, with competition in the form of advanced wound closure, whether surgical sealants, glues, hemostats, and even other mechanical wound closure. Novel wound closure technologies have decidedly gained enough credibility in clinical practice to displace volume in sutures and staples.

Sutures and Staples Are Not Fading…

Manufacturers of sutures and staples have not sat idly and watched their share erode. Indeed, the development of bioresorbable sutures and other novel suture types, the development of sophisticated stapling and suturing endoscopic instrumentation and other developments have begun to erode the share loss. Consequently, the shift “away” from sutures and staples has ebbed, such that the aggregate swing in market shares is no more than 3% compared to the swing projected three years ago of nearly 7% (see link).

The vast majority of sutures, staples, and endostaples are used to close procedures involving acute surgical wounds. Typically, chronic wounds do not involve the use of sutures and staple products unless some degree of surgical intervention is employed to remove necrotic tissue or to create a new acute wound bed to aid healing.

Sutures are classified as absorbable or non-absorbable; monofilament, multifilament or braided; and natural or synthetic. Absorbable or non-absorbable describes the suture’s effective life within tissue. Absorbable sutures lose the majority of their tensile strength within 60 days after use. Non-absorbable sutures are resistant to living tissue and do not break down. Monofilament, multifilament, and braided describe the structure or configuration of the suture based on the number of strands used to manufacture the product. Natural or synthetic refers to the origin of the suture. Natural suture materials include surgical gut, chromic gut, catgut and silk. Catgut is made from the natural collagen fibers found in the intestine of sheep, goats, cattle, hogs and horses. (It was never made from the gut of cats.) It is debatable whether catgut should continue to be used for suturing wounds, since cotton is cheaper and cotton or synthetic threads are less likely to cause infection. Synthetic suture materials include nylon, polyester, stainless steel, polypropylene, polyglycolic acid (PGA), polyglycolide-co-caprolactone (PGCL), and polydioxanone.

Suture products consist of two component parts, the needle and the suture. These can be found in a wide range of sizes and types, made of a range of materials, and the method of attachment of the suture to the needle can involve a variety of methods. Sutures are divided into braided and monofilament categories. Braided sutures are typically more pliable than monofilament and exhibit better knot security. Monofilament sutures are wirier and may require a more secure knot; however, they cause less tissue drag than braided sutures, a characteristic that is especially important in cardiovascular, ophthalmic and neurological surgery

Stapler devices are an evolution of suture technology. The goal of stapler products is to avoid infection and make the wound closure procedure easier and faster. Staples are made of stainless steel and biomaterials and are used to join internal tissues, reconstruct or seal off organs, remove diseased tissue, occlude blood vessels, and close skin incisions and lacerations. They are primarily used during surgery as internal and/or external closure devices.

Staples are available in an assortment of sizes and features and stapler devices have been developed for specific procedures as well as for multiple uses.

Internal staplers are used to approximate (or close) internal tissues and organs. The devices may be reusable or disposable. Some disposable staplers may be reloaded several times during the course of a single patient surgical procedure, before being discarded.

The most recent internal staplers are used to perform minimally invasive surgical procedures. These allow the surgeon to endoscopically secure internal wounds instead of having to operate through an open procedure. Moreover, internal biodegradable staples obviate the need for staple removal. Such staples are ideally suited to laparoscopic surgery and are delivered via procedure-specific laparoscopic instruments. However, most staples are still made of stainless steel and when used for internal stapling procedures, whether open or laparoscopic, are not removed after healing. Skin staples are removed after the incision is healed.

Probably the major benefit of staples is that they can be applied more rapidly than sutures and can be placed precisely without requiring the skill necessary for suturing. This also means increased safety for the patient, and patients can often be discharged more rapidly if procedures are stapled rather than sutured.

While cosmetically acceptable results are usually obtained, staplers normally are not used in highly visible areas such as the face. Here, surgeons will still close by hand to minimize any scarring. In many skin closure procedures, sutures have begun to be replaced by cyanoacrylate glues. However, the ideal alternative to suturing has not yet been developed; for example, cyanoacrylate glues used for external skin closure are only one-fifth as strong as sutures.

Sealants and glues are emerging as important adjunctive tools for sealing staple and suture lines, and some of these products also are being employed as general hemostatic agents to control bleeding in the surgical field. Manufacturers have also developed surgical sealants and glues that are designed for specific procedures – particularly those in which staples and sutures are difficult to employ or where additional reinforcement of the internal suture/staple line provides an important safety advantage.

Surgical sealants are made of synthetic or naturally occurring materials and are commonly used with staples or sutures to help completely seal internal and external incisions after surgery. In this capacity, they are particularly important for lung, spinal, and gastrointestinal operations, where leaks of air, cerebrospinal fluid, or blood through the anastomosis can cause numerous complications. Limiting these leaks results in reduced mortality rates, less post-operative pain, shorter hospital stays for patients, and decreased health care costs.

Although some form of suturing wounds has been used for thousands of years, sutures and staples can be troublesome. There are procedures in which sutures are too large or clumsy to place effectively, and locations in which it is difficult for the surgeon to suture. Moreover, sutures can lead to complications, such as intimal hyperplasia, in which cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point. This increases the risk of a blood clot forming and obstructing blood flow. In addition, sutures and staples may trigger an immune response, leading to inflamed tissue that also increases the risk of a blockage. Finally, as mentioned above, sutured and stapled internal incisions may leak, leading to dangerous post-surgical complications.

These are some of the reasons why surgical adhesives are becoming increasingly popular, both for use in conjunction with suture and staples and on a stand-alone basis. As a logical derivative, surgeons want a sealant product that is strong, easy-to-use and affordable, while being biocompatible and resorbable. In reality, it is difficult for manufacturers to meet all of these requirements, particularly with biologically active sealants, which tend to be pricey. Thus, for physicians, there is usually a trade-off to consider when deciding whether or not to employ these products.

Surgical sealants, glues, and hemostats can be divided into several different categories based on their primary components and/or their intended use.

The following is excerpted from sections of Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”, published by MedMarket Diligence, LLC.

Sealants and glues in wound closure may be comprised of naturally-occurring (bioactive) ingredients (including from human or animal) or may be synthetic in origin. Many bioactives are comprised primarily of fibrin sealant, give its evolutionary design in stopping bleeding and sealing wounds. Bioactive sealants offer the benefit of well documented performance with lack of toxicity, but with the existing sealants on the market, the strength of the closure provided falls somewhat short of what is needed for sealants to be used autonomously in all but the least challenging closure conditions. For this reason, a wide range of other biologically active agents with higher sealant strength are in various phases of evaluation (See “Gecko feet, mussel shells and other sticky things” at link).

Bioactive sealants that on the market and in development are detailed at link.

Compared to biologically active sealants containing fibrin and other human- or animal-derived products, synthetic sealants represent a much larger segment of the sealant market in terms of the number of competitors, variety of products, and next-generation products in development. Non-active synthetic sealants do not contain ingredients such as fibrin that actively mediate the blood clotting cascade, rather they act as mechanical hemostats, binding with or adhering to the tissues to help stop or prevent active bleeding during surgery.

Synthetic sealants that are on the market and in development are detailed at link.

For example, the two graphics below illustrate the wound closure markets in Germany and the United Kingdom. To have fully compared the markets in these two countries aside from differences in population, we might have presented per capita values in the sales, but even without doing so it is clear that relative sizes and growth rates in the two countries are sufficiently different to warrant attention in local efforts to market these products.

Source: “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”, Report #S192; published by MedMarket Diligence, LLC. (Note: This report has been superceded by the August 2016 Report #S290.)

Of late, I have needed to re-emphasize the difference between absolute and relative growth in medtech markets (and its importance). So, here it is again, this time regarding surgical sealants and other wound closure products.

The lowest relative rate of growth in this industry is the well-established sutures and staples segment. Sales of these products globally, even supported by innovations in bioresorbables and laparoscopic delivery technologies, are only growing at a 5.6% compound annual growth rate from 2013 to 2018. By comparison, growth of sales of surgical glues and sealants is at 9.4% for 2013-2018.

But from an absolute sales growth point of view, sales of sutures and staples will go from $5.2 billion to $6.9 billion, or absolute growth of $1.7 billion. Simultaneously, the relatively high growth in surgical glues and sealants translates to the absolute growth from 2013 to 2018 of only $0.9 billion.

Biologically active sealants typically contain various formulations of fibrin and/or thrombin, either of human or animal origin, which mimic or facilitate the final stages of the coagulation cascade. The most common consist of a liquid fibrin sealant product in which fibrinogen and thrombin are stored separately as a frozen liquid or lyophilized powder. Before use, both components need to be reconstituted or thawed and loaded into a two-compartment applicator device that allows mixing of the two components just prior to delivery to the wound. Because of the laborious preparation process, these products are not easy to use. However, manufacturers have been developing some new formulations designed to make the process more user friendly.

Selected Biologically Active Sealants, Glues, and Hemostats

Company

Product Name

Description/ (Status*)

Asahi Kasei Medical

CryoSeal FS System

Fibrin sealant system comprising an automated device and sterile blood processing disposables that enable autologous fibrin sealant to be prepared from a patient's own blood plasma in about an hour.

Baxter

Artiss

Fibrin sealant spray

Baxter

Tisseel

Biodegradable fibrin sealant made of human fibrinogen and human thrombin. For oozing and diffuse bleeding.

Evicel is a new formulation of the previously available fibrin sealant Quixil (EU)/Crosseal (US). Does not contain the antifibrinolytic agent tranexamic acid, which is potentially neurotoxic, nor does it contain synthetic or bovine aprotinin, which reduces potential for hypersensitivity reactions.

J&J/Ethicon

Evarrest

Absorbable fibrin sealant patch comprised of flexible matrix of oxidized, regenerated cellulose backing under a layer of polyglactin 910 non-woven fibers and coated on one side with human fibrinogen and thrombin.

Company is working with Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) to develop a sheet-type surgical fibrin sealant. Product combines KAKETSUKEN's recombinant thrombin and fibrinogen technology with Teijin's high-performance fiber technology to create the world's first recombinant fibrin sealant on a bioabsorbable, flexible, nonwoven electrospun fiber sheet.

The Medicines Company (TMC)

Raplixa (formerly Fibrocaps)

Sprayable dry-powder formulation of fibrinogen and thrombin to aid in hemostasis during surgery to control mild or moderate bleeding.

The Medicines Company (TMC)

In development: Fibropad patch

FDA accepted company's BLA application for Fibrocaps in April 2014 and set an action date (PDUFA) in 2015. In November 2013, the European Medicines Agency agreed to review the firm's EU marketing authorization application. Status update in report #S192.

Vascular Solutions

D-Stat Flowable

Thick, but flowable, thrombin-based mixture to prevent bleeding in the subcutaneous pectoral pockets created during pacemaker and ICD implantations.